Buprenorphine (International Non-proprietary Name for N-cyclopropylmethyl-7α-[1-(S)-hydroxy-1,2,2-trimethylpropyl]6,14-endoethano-6,7,8,14-tetrahydro-nororipavine) has been shown in clinical trials to be a potent opiate partial agonist analgesic lacking the psychotomimetic effects found with other opiate analgesics. Buprenorphine effectively relieves moderate to severe pain in doses of 0.1 mg or more administered either parenterally or sublingually. The optimum therapeutic range for single doses is 0.3 mg–0.6 mg by injection and 0.2 mg–0.8 mg for sublingual tablets.
In animal tests and in man buprenorphine has been shown to have both agonist (morphine-like) and antagonist properties. However from direct dependence studies in animals and in man it has been concluded that buprenorphine does not produce significant physical dependence, as indicated by animal self administration studies and by the measurement of euphorigenic effects in human post addicts. However, buprenorphine suffers from side effects typical of opiate agonists such as nausea and vomiting, constipation and respiratory depression in some patients, although there is a ceiling to its effects on respiratory depression as a direct consequence of its partial agonist properties.
Naloxone (International Non-proprietary Name for 1-N-allyl-14-hydroxynorhydromorphinone) is a narcotic antagonist which has been incorporated into oral and sublingual preparations of various opioids in order to protect the preparations from parenteral abuse, whilst maintaining the analgesic effect of the opioid.
GB-A-2150832 describes analgesic compositions in sublingual or parenteral dosage form comprising an active dose of buprenorphine and an amount of naloxone sufficient to prove aversive to a narcotic addict by parenteral administration but insufficient to compromise the analgesic action of the buprenorphine. Preferably the parenteral dosage form contains naloxone and buprenorphine within the weight ratio of 1:3 to 1:1 and the sublingual form within the ratio 1:2 to 2:1.
Naltrexone (International Non-proprietary Name for 1-N-cyclopropylmethyl-14-hydroxynordihydro-morphinone) is a pure opiate antagonist which, when administered orally (50 mg/day) as a maintenance drug for opiate addicts, blocks the effects of self-administered opiates and this contributes to the extinction of drug craving.
Nalmefene (International Non-Proprietary Name for (5)-17-(cyclopropylmethyl)-4,5-epoxy-6-methylene-morphinan-3,14-diol) is a structural analogue of naltrexone with opiate antagonist activity.
GB-A-2167633 describes an analgesic composition in parenteral or sublingual unit dosage form comprising an active dose of buprenorphine and an amount of naltrexone sufficient to prove aversive to a narcotic addict by parenteral administration but insufficient to compromise the analgesic action of the buprenorphine wherein the dose of buprenorphine in the parenteral form is from about 0.3 mg to about 0.6 mg and in the sublingual form from about 0.1 mg to about 0.4 mg and the weights of buprenorphine to naltrexone for the parenteral form are within the ratio of 12:1 to 3:1 and for the sublingual form are within the ratio 4:1 to 1:1.